Palbociclib, 6-Acetyl-8-cyclopentyl-5-methyl-2-[[5-(1-piperazinyl)-2-pyridinyl]amino]pyrido[2,3-d]pyrimidin-7(8H)-one, has the following chemical structure:

Palbociclib is a kinase inhibitor indicated in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease.
Palbociclib was described in WO 2003/062236. WO 2005/005426 described crystalline forms of isethionate, mesylate, dimesylate, HCl and di-HCl salts of Palbociclib. Further crystalline forms and amorphous form of Palbociclib HCl are described in WO 2016/066420. WO 2016/092442 and WO 2016/090257 describe crystalline forms of Palbociclib salts including phosphate, acetate, lactate, maleate, fumarate, citrate, succinate, L-tartarate, glutarate, adipate, glyconate, diesylate, hippurate, esylate and isethionate.
WO 2014/128588 discusses two crystalline forms, denominated A and B of Palbociclib.
Polymorphism, the occurrence of different crystalline forms, is a property of some molecules and molecular complexes. A single molecule may give rise to a variety of polymorphs having distinct crystal structures and physical properties like melting point, thermal behaviors (e.g. measured by thermogravimetric analysis—“TGA”, or differential scanning calorimetry—“DSC”), X-ray diffraction pattern, infrared absorption fingerprint, and solid state (13C) NMR spectrum. One or more of these techniques may be used to distinguish different polymorphic forms of a compound.
Different salts and solid state forms (including solvated forms) of an active pharmaceutical ingredient may possess different properties. Such variations in the properties of different salts and solid state forms and solvates may provide a basis for improving formulation, for example, by facilitating better processing or handling characteristics, changing the dissolution profile in a favorable direction, or improving stability (polymorph as well as chemical stability) and shelf-life. These variations in the properties of different salts and solid state forms may also offer improvements to the final dosage form, for instance, if they serve to improve bioavailability. Different salts and solid state forms and solvates of an active pharmaceutical ingredient may also give rise to a variety of polymorphs or crystalline forms, which may in turn provide additional opportunities to assess variations in the properties and characteristics of a solid active pharmaceutical ingredient.
Discovering new solid state forms and solvates of a pharmaceutical product may yield materials having desirable processing properties, such as ease of handling, ease of processing, storage stability, and ease of purification or as desirable intermediate crystal forms that facilitate conversion to other polymorphic forms. New solid state forms of a pharmaceutically useful compound can also provide an opportunity to improve the performance characteristics of a pharmaceutical product. It enlarges the repertoire of materials that a formulation scientist has available for formulation optimization, for example by providing a product with different properties, e.g., a different crystal habit, higher crystallinity, or polymorphic stability, which may offer better processing or handling characteristics, improved dissolution profile, or improved shelf-life (chemical/physical stability). For at least these reasons, there is a need for additional solid state forms (including solvated forms) of Palbociclib.
Processes for preparation of Palbociclib were disclosed in WO 2003/062236, WO 2005/005426 and WO 2014/128588. The process development of Palbociclib is also discussed in Org. Process Res & Dev. 2016, 20, 1191-1202 (Duan et al.), 1203-1216 (Sutherland et al.) and 1217-1226 (Chekal et al).
However, Palbociclib obtained by prior art processes may typically contain the compound, 2-{[5-(1-piperazinyl)-2-pyridinyl]amino}-8-cyclopentyl-5-methylpyrido[2,3-d]pyrimidin-7(8H)-one, (herein designated as “Impurity A”) as an impurity which is represented by the following structural formula:

Impurity A is difficult to remove from the desired Palbociclib.
For at least these reasons, there is a need to develop robust processes for preparation of Palbociclib.